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1. 江苏大学附属人民医院耳鼻咽喉科,江苏 镇江 212000
2. 南京中医药大学附属常州市中医院耳鼻咽喉科,江苏 常州 21300
[ "郑丹苹(ORCID: 0000-0002-0215-8237),硕士在读 E-mail: ncuzdp@163.com" ]
钱 炜(ORCID: 0000-0002-2385-7029),博士,教授,江苏大学附属人民医院(临床医学院)副院长,江苏省特聘医学专家E-mail: dwqian@yahoo.com
收稿:2022-02-14,
修回:2022-05-03,
纸质出版:2022-05-30
移动端阅览
郑丹苹, 钱炜, 郑楚杰. T-G-C纳米材料联合声动力学治疗喉癌的研究[J]. 中国癌症杂志, 2022,32(5):436-444.
Danping ZHENG, Wei QIAN, Chujie ZHENG. A study on T-G-C nanomaterials combined with sonodynamic therapy in the treatment of laryngeal cancer[J]. China Oncology, 2022, 32(5): 436-444.
郑丹苹, 钱炜, 郑楚杰. T-G-C纳米材料联合声动力学治疗喉癌的研究[J]. 中国癌症杂志, 2022,32(5):436-444. DOI: 10.19401/j.cnki.1007-3639.2022.05.009.
Danping ZHENG, Wei QIAN, Chujie ZHENG. A study on T-G-C nanomaterials combined with sonodynamic therapy in the treatment of laryngeal cancer[J]. China Oncology, 2022, 32(5): 436-444. DOI: 10.19401/j.cnki.1007-3639.2022.05.009.
背景与目的:
喉癌是目前难治性的耳鼻咽喉科恶性肿瘤
常采用放化疗联合手术治疗
但该
疗法对患者的5年生存率和死亡率改善不大
且常伴随喉部功能丧失和药物抵抗。本研究旨在探索纳米声敏剂T-G-C颗粒介导的声动力学治疗(sonodynamic therapy
SDT)在抑制人喉癌细胞中的作用
为喉癌的治疗提供一种新型非侵入性的治疗方法。
方法:
基于已经合成的T-G-C纳米材料
在激光扫描共聚焦显微镜下评价Tu686细胞摄取纳米材料的情况
在超声存在下用细胞计数试剂盒-8(cell counting kit-8
CCK-8)和Annexin
&
#x02164;-异硫氰酸荧光素(fluorescein isothiocyanate
FITC)试剂评估细胞存活和凋亡的情况。构建人喉癌细胞系Tu686的BALB/c裸小鼠移植瘤模型
通过注射不同类型药物和进行肿瘤区域超声辐照
在治疗期间记录小鼠体重和肿瘤变化
分析比较治疗效果;应用H-E、TUNEL、Ki-67及DHE染色等方法比较肿瘤细胞凋亡和活性氧(reactive oxygen species
ROS)产生情况。
结果:
纳米材料与细胞温育24 h未见明显毒性
仅在超声刺激下导致细胞存活率下降
细胞主要以早期凋亡和晚期凋亡为主。动物实验中仅在第1、3、5和7天经过瘤内注射药物和超声处理
发现仅T-G-C+超声组小鼠肿瘤增长显著被抑制
抑瘤率为100%
且经16 d的治疗
肿瘤区域经超声辐照后可见明显的红色荧光
证实抑瘤作用的核心是ROS的产生。
结论:
生物相容性高的T-G-C纳米颗粒在超声刺激时
激发了SDT和压电治疗的协同作用
通过ROS促进喉癌细胞早期和晚期凋亡
为喉癌提供了一种联合治疗方法
有望促进多学科治疗在耳鼻咽喉科中的应用。
Background and purpose:
Laryngeal cancer is a refractory malignant tumor in otolaryngology. Radiotherapy and chemotherapy combined with surgery are often used
however
this treatment method has little improvement on the 5-year survival rate and mortality of patients
and is often accompanied by loss of laryngeal function and drug resistance. This study aimed to explore the effect of sonodynamic therapy (SDT) mediated by nanoacoustic sensitizer T-G-C particles on inhibiting human laryngeal cancer cells
and to provide a new non-invasive treatment for laryngeal cancer.
Methods:
Based on the synthesized T-G-C nanomaterials
the uptake of nanomaterials by Tu686 cells was evaluated under confocal laser scanning microscope
and the cell survival and apoptosis were evaluated by cell counting kit-8 (CCK-8) and Annexin
&
#x02164;- fluorescein isothiocyanate (FITC) reagent in the presence of ultrasound. BALB/c nude mouse xenograft model was established. The weight and tumor changes of mice were recorded during the treatment by injecting different types of drugs and ultrasonic irradiation in the tumor area
and the treatment effects were analyzed and compared. The apopto
sis and necrosis of tumor cells and the production of reactive oxygen species (ROS) were compared by H-E
TUNEL
Ki-67 and DHE stainings.
Results:
Nanomaterials and cells incubated for 24 hours had no obvious toxicity
only led to the decline of cell survival rate under ultrasonic stimulation
and the cells showed mainly early apoptosis and late apoptosis. In the animal experiment
only after intratumoral injection of drugs and ultrasound treatment on the 1st
3rd
5th and 7th days
the tumor growth of mice in T-G-C+ultrasound group was significantly inhibited
and the tumor inhibition rate is 100%. After 16 d of treatment
obvious red fluorescence could be seen in the tumor area after ultrasound irradiation
which demonstrated that the core of tumor inhibition was the production of ROS.
Conclusion:
Biocompatible T-G-C nanoparticles stimulate the synergy of SDT and piezoelectric therapy when stimulated by ultrasound
and promote the early and late apoptosis of laryngeal cancer cells through ROS
which provides a combined treatment method for laryngeal cancer and promotes the application of multidisciplinary therapy in department of otolaryngology.
MILLER K D , SIEGEL R L , LIN C C , et al . Cancer treatment and survivorship statistics, 2016 [J ] . CA A Cancer J Clin , 2016 , 66 ( 4 ): 271 - 289 . DOI: 10.3322/caac.21349 http://doi.org/10.3322/caac.21349 http://doi.wiley.com/10.3322/caac.21349 http://doi.wiley.com/10.3322/caac.21349
ZWIRNER K , THORWARTH D , WINTER R M , et al . Voxel-wise correlation of functional imaging parameters in HNSCC patients receiving PET/MRI in an irradiation setup [J ] . Strahlentherapie Und Onkologie , 2018 , 194 ( 8 ): 719 - 726 . DOI: 10.1007/s00066-018-1292-4 http://doi.org/10.1007/s00066-018-1292-4 https://doi.org/10.1007/s00066-018-1292-4 https://doi.org/10.1007/s00066-018-1292-4
FAKHRY C , WESTRA W H , LI S G , et al . Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial [J ] . J Natl Cancer Inst , 2008 , 100 ( 4 ): 261 - 269 . DOI: 10.1093/jnci/djn011 http://doi.org/10.1093/jnci/djn011 https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djn011 https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djn011
LIU Q H , WANG X B , WANG P , et al . Comparison between sonodynamic effect with protoporphyrin Ⅸ and hematoporphyrin on sarcoma 180 [J ] . Cancer Chemother Pharmacol , 2007 , 60 ( 5 ): 671 - 680 . DOI: 10.1007/s00280-006-0413-4 http://doi.org/10.1007/s00280-006-0413-4 http://link.springer.com/10.1007/s00280-006-0413-4 http://link.springer.com/10.1007/s00280-006-0413-4
JOHNSON D E , BURTNESS B , LEEMANS C R , et al . Head and neck squamous cell carcinoma [J ] . Nat Rev Dis Primers , 2020 , 6 : 92 . DOI: 10.1038/s41572-020-00224-3 http://doi.org/10.1038/s41572-020-00224-3 https://doi.org/10.1038/s41572-020-00224-3 https://doi.org/10.1038/s41572-020-00224-3
FERLAY J , COLOMBET M , SOERJOMATARAM I , et al . Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods [J ] . Int J Cancer , 2019 , 144 ( 8 ): 1941 - 1953 . DOI: 10.1002/ijc.31937 http://doi.org/10.1002/ijc.31937 https://onlinelibrary.wiley.com/doi/10.1002/ijc.31937 https://onlinelibrary.wiley.com/doi/10.1002/ijc.31937
ISAYEVA T , LI Y F , MASWAHU D , et al . Human papillomavirus in non-oropharyngeal head and neck cancers: a systematic literature review [J ] . Head Neck Pathol , 2012 , 6 ( Suppl 1 ): S104 - S120 .
STEIN A P , SAHA S , KRANINGER J L , et al . Prevalence of human papillomavirus in oropharyngeal cancer [J ] . Cancer J , 2015 , 21 ( 3 ): 138 - 146 . DOI: 10.1097/PPO.0000000000000115 http://doi.org/10.1097/PPO.0000000000000115 https://journals.lww.com/00130404-201505000-00002 https://journals.lww.com/00130404-201505000-00002
NOCINI R , MOLTENI G , MATTIUZZI C , et al . Updates on larynx cancer epidemiology [J ] . Chin J Cancer Res , 2020 , 32 ( 1 ): 18 - 25 . DOI: 10.21147/j.issn.1000-9604.2020.01.03 http://doi.org/10.21147/j.issn.1000-9604.2020.01.03 http://article.cjcrcn.org/en/article/doi/10.21147/j.issn.1000-9604.2020.01.03?viewType=HTML http://article.cjcrcn.org/en/article/doi/10.21147/j.issn.1000-9604.2020.01.03?viewType=HTML
GROOME P A , O'SULLIVAN B , IRISH J C , et al . Management and outcome differences in supraglottic cancer between Ontario, Canada, and the Surveillance, Epidemiology, and End Results areas of the United States [J ] . J Clin Oncol , 2003 , 21 ( 3 ): 496 - 505 . DOI: 10.1200/JCO.2003.10.106 http://doi.org/10.1200/JCO.2003.10.106 https://ascopubs.org/doi/10.1200/JCO.2003.10.106 https://ascopubs.org/doi/10.1200/JCO.2003.10.106
ZIENTAL D , CZARCZYNSKA-GOSLINSKA B , MLYNARCZYK D T , et al . Titanium dioxide nanoparticles: prospects and applications in medicine [J ] . Nanomaterials (Basel) , 2020 , 10 ( 2 ): 387 . DOI: 10.3390/nano10020387 http://doi.org/10.3390/nano10020387 https://www.mdpi.com/2079-4991/10/2/387 https://www.mdpi.com/2079-4991/10/2/387
CHEN B , ZHENG R N , LIU D , et al . The tumor affinity of chlorin e6 and its sonodynamic effects on non-small cell lung cancer [J ] . Ultrason Sonochemistry , 2013 , 20 ( 2 ): 667 - 673 . DOI: 10.1016/j.ultsonch.2012.09.008 http://doi.org/10.1016/j.ultsonch.2012.09.008 https://linkinghub.elsevier.com/retrieve/pii/S1350417712001915 https://linkinghub.elsevier.com/retrieve/pii/S1350417712001915
黄苏苏 , 谢波 , 凌家俊 , 等 . 二氢卟吩e6磁性声敏纳米脂质体的制备及质量评价 [J ] . 中国实验方剂学杂志 , 2017 , 23 ( 8 ): 21 - 26 .
HUANG S S , XIE B , LING J J , et al . Preparation and quality evaluation of chlorin e6 magnetic sound sensitive nano-liposomes [J ] . Chin J Exp Tradit Med Formulae , 2017 , 23 ( 8 ): 21 - 26 .
MCHALE A P , CALLAN J F , NOMIKOU N , et al . Sonodynamic therapy: concept, mechanism and application to cancer treatment [J ] . Adv Exp Med Biol , 2016 , 880 : 429 - 450 .
QIAN X Q , ZHENG Y Y , CHEN Y . Micro/nanoparticle-augmented sonodynamic therapy (SDT): breaking the depth shallow of photoactivation [J ] . Adv Mater , 2016 , 28 ( 37 ): 8097 - 8129 . DOI: 10.1002/adma.201602012 http://doi.org/10.1002/adma.201602012 https://onlinelibrary.wiley.com/doi/10.1002/adma.201602012 https://onlinelibrary.wiley.com/doi/10.1002/adma.201602012
ROSENTHAL I , SOSTARIC J Z , RIESZ P . Sonodynamic therapy: a review of the synergistic effects of drugs and ultrasound [J ] . Ultrason Sonochem , 2004 , 11 ( 6 ): 349 - 363 . DOI: 10.1016/j.ultsonch.2004.03.004 http://doi.org/10.1016/j.ultsonch.2004.03.004 https://linkinghub.elsevier.com/retrieve/pii/S1350417704000793 https://linkinghub.elsevier.com/retrieve/pii/S1350417704000793
SON S , KIM J H , WANG X W , et al . Multifunctional sonosensitizers in sonodynamic cancer therapy [J ] . Chem Soc Rev , 2020 , 49 ( 11 ): 3244 - 3261 . DOI: 10.1039/C9CS00648F http://doi.org/10.1039/C9CS00648F http://xlink.rsc.org/?DOI=C9CS00648F http://xlink.rsc.org/?DOI=C9CS00648F
张彦军 , 李增发 . 声动力学疗法的抗癌机理 [J ] . 医疗装备 , 1998 , 11 ( 9 ): 1 - 3 .
ZHANG Y J , LI Z F . Analysis of the mechanism of SDT in anti-tumor effect [J ] . Med Equip , 1998 , 11 ( 9 ): 1 - 3 .
景姣姣 , 王新 , 李倩玉 , 等 . 声敏剂的构效关系研究进展 [J ] . 中国药房 , 2017 , 28 ( 28 ): 4000 - 4003 .
JING J J , WANG X , LI Q Y , et al . Research progress of structure-activity relationship of sound sensitive agents [J ] . China Pharm , 2017 , 28 ( 28 ): 4000 - 4003 .
STEUER C E , EL-DEIRY M , PARKS J R , et al . An update on larynx cancer [J ] . CA Cancer J Clin , 2017 , 67 ( 1 ): 31 - 50 . DOI: 10.3322/caac.21386 http://doi.org/10.3322/caac.21386 http://doi.wiley.com/10.3322/caac.21386 http://doi.wiley.com/10.3322/caac.21386
KITAMURA N , SENTO S , YOSHIZAWA Y , et al . Current trends and future prospects of molecular targeted therapy in head and neck squamous cell carcinoma [J ] . Int J Mol Sci , 2020 , 22 ( 1 ): 240 . DOI: 10.3390/ijms22010240 http://doi.org/10.3390/ijms22010240 https://www.mdpi.com/1422-0067/22/1/240 https://www.mdpi.com/1422-0067/22/1/240
LOO C , LOWERY A , HALAS N , et al . Immunotargeted nanoshells for integrated cancer imaging and therapy [J ] . Nano Lett , 2005 , 5 ( 4 ): 709 - 711 . DOI: 10.1021/nl050127s http://doi.org/10.1021/nl050127s https://pubs.acs.org/doi/10.1021/nl050127s https://pubs.acs.org/doi/10.1021/nl050127s
ALI I , RAHIS-UDDIN , SALIM K , et al . Advances in nano drugs for cancer chemotherapy [J ] . Curr Cancer Drug Targets , 2011 , 11 ( 2 ): 135 - 146 . DOI: 10.2174/156800911794328493 http://doi.org/10.2174/156800911794328493 http://www.eurekaselect.com/openurl/content.php?genre=article&issn=1568-0096&volume=11&issue=2&spage=135 http://www.eurekaselect.com/openurl/content.php?genre=article&issn=1568-0096&volume=11&issue=2&spage=135
张传忠 . 压电材料的发展及应用 [J ] . 压电与声光 , 1993 , 15 ( 3 ): 64 - 70 .
ZHANG C Z . Development of piezoelectric materials and their applications [J ] . Piezoelectrics Acoustooptics , 1993 , 15 ( 3 ): 64 - 70 .
田中华 , 黄明春 , 冷静 . 纳米声敏剂在声动力疗法中的研究进展 [J ] . 中国现代应用药学 , 2019 , 36 ( 8 ): 1018 - 1022 .
TIAN Z H , HUANG M C , LENG J . Advances of nano-sonosensitizers in sonodynamic therapy [J ] . Chin J Mod Appl Pharm , 2019 , 36 ( 8 ): 1018 - 1022 .
KAMINSKYY V O , ZHIVOTOVSKY B . Free radicals in cross talk between autophagy and apoptosis [J ] . Antioxid Redox Signal , 2014 , 21 ( 1 ): 86 - 102 . DOI: 10.1089/ars.2013.5746 http://doi.org/10.1089/ars.2013.5746 http://www.liebertpub.com/doi/10.1089/ars.2013.5746 http://www.liebertpub.com/doi/10.1089/ars.2013.5746
堵建岗 , 劳力民 . 光动力学结合声动力学治疗对小鼠鳞癌细胞超微结构的影响 [J ] . 激光生物学报 , 2015 , 24 ( 4 ): 331 - 334 .
DU J G , LAO L M . Effect of sono-photodynamic combination therapy on the ultrastructure of squamous cell carcinoma in mice [J ] . Acta Laser Biol Sin , 2015 , 24 ( 4 ): 331 - 334 .
ZHAO Y , HU X B , LIU Y J , et al . ROS signaling under metabolic stress: cross-talk between AMPK and AKT pathway [J ] . Mol Cancer , 2017 , 16 ( 1 ): 79 . DOI: 10.1186/s12943-017-0648-1 http://doi.org/10.1186/s12943-017-0648-1 http://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-017-0648-1 http://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-017-0648-1
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